Serine proteases are members of a family of proteolytic enzymes characterized by the presence of a cardinal serine in the catalytic site. They play important metabolic and cellular functions. Blood cells in particular are known to express serine proteases, with each protease playing a specific role in acute and chronic inflammation and in tissue remodeling. Eosinophil blood cells are involved in the modulation of respiratory immune responses, hypersensitivity, and tissue remodeling.
A serine protease gene (esp-1) from a human eosinophil has recently been cloned and characterized from patients with eosinophilia. See Inoue et al., Biochem. Biophys. Res. Commun. 252: 307–312 (1998) and Inoue et al., Biochem. Biophys. Res. Commun. 266: 564–568 (1999). Eosinophils are widely distributed within the human body and are found in the respiratory system, in skeletal muscle, and in cartilage. The esp-1 enzyme was identified as a serine protease by its homology with known serine proteases. Id., Davis et al., Adv. Enzymol. 48: 277–318 (1979), and Kohno et al., Biochem. Biophys. Res. Commun. 245: 658–665. Esp-1 mRNA was detected in a number of tissues, but only weakly in peripheral blood leukocytes, and not on kidney nor skeletal muscle, but highly expressed in testis. Therefore, it was expected that this particular serine protease is involved in fertilization processes. See Inoue (1998), supra. The genomic sequence was identified on chromosome 16, at p13.3. An expressed but presumably non-functional splicing variant was also reported. See Inoue (1999), supra. An additional esp-1 protein designated testisin was reported and is expected to also relate to human fertility. See Hooper et al., Cancer Res. 59: 3199–3205 (1999). Because of the involvement of serine proteases in a variety of biological functions, there is a continuing need to identify additional eosinophil-derived serine proteases which can be regulated to provide therapeutic effects.